P1283: ANTI-CD19 CHIMERIC ANTIGEN RECEPTOR THERAPY FOLLOWED BY UMBILICAL CORD BLOOD TRANSPLANTATION IN PEDIATRIC RELAPSED OR REFRACTORY ACUTE LYMPHOBLASTIC LEUKEMIA: GOOD SURVIVAL AND LESS GVHD
Authors: Fang Liu
Journal: HemaSphere (2023)

Topic: 22. Stem cell transplantation - Clinical Background: Autologous T cells engineered to express a CD19-specific chimeric antigen receptor (CAR) have been confirmed impressive efficacy in relapsed/refractory(R/R) B-cell acute lymphoblastic leukemia (B-ALL), but some patients relapsed quickly who may benefit from bridging to allogeneic stem cell transplantation (HSCT). However, for patients after CAR-T therapy followed by haploid-HSCT, minimal residual disease (MRD) positivity at transplantation is an independent adverse prognostic factor. Umbilical cord blood transplantation (UCBT) has been proven with less cancer relapse and higher survival in pediatric ALL, especially for the MRD-positive patients before transplant. Then what is the efficacy and safety of UCBT for pediatric R/R B-ALL after CAR-T therapy? Could these MRD-positive children benefit from UCBT? In our study, we tried to answer the questions. Aims: To investigate the efficacy and safety of UCBT after Anti-CD19 CAR-T in pediatric R/R B-ALL. Methods: We retrospectively analyzed 30 patients aged <21 years with R/R B-ALL who underwent UCBT at the Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences between Jan 2018 and Apr 2022. Among them, 15 patients were treated with CAR-T therapy before UCBT (the CAR-T group), and the remaining 15 patients received only salvage chemotherapy before UCBT (the Non-CAR-T group). In the CAR-T group, all the patients obtained CR but 5 children remained MRD-positive (by high-resolution flow cytometry) including 1 case who relapsed again before the transplant. The median interval from CAR-T infusion to UCBT was 66 days (range, 44-149 days). While in the Non-CAR-T group, 2 children remained MRD-positive at the time of transplant. Both groups underwent a myeloablative conditioning regimen based of Cyclophosphamide and Busulfan. Ciclosporin and mycophenolate mofetil were used for graft-versus-host disease (GVHD) prophylaxis. All surviving patients were followed until Dec 31, 2022, and the median follow-up was 19.5 months (range, 4 to 59 months). Results: Patient demographic and baseline clinical characteristics are summarized in Table 1. The Non-CAR-T group had more boys (P=.020), but more children were suffering MRD-positive at transplant in the CAR-T group (P=.038). All patients achieved sustained engraftment of both neutrophils and platelets, with complete donor chimerism confirmed at 30 days. The median time to neutrophil engraftment was 19 days (range, 13 to 28 days) in the CAR-T group and 18 days (range, 14 to 43 days) in the Non-CAR-T group (P =.284), respectively. While the median time to platelets engraftment was 36 days (range, 21 to 116 days) and 34 days (range, 25 to 108 days) in 2 groups (P =.633), respectively. The cumulative incidences of grade III-IV acute GVHD in CAR-T group was significantly lower than that of the Non-CAR-T group (0% versus 26.7% ± 11.4%, P =.035). 4 patients relapsed after UCBT including 1 boy in the CAR-T group and 3 boys in the Non-CAR-T group. The 2-year cumulative incidence of relapse (CIR) was slightly lower in the CAR-T group but not significantly different (8.3% ± 8.0% versus 23.1% ± 11.5%, P =.243). In the CAR-T group, the probabilities of 2-year overall survival and leukemia-free survival were 85.7% ± 13.2%, 91.7% ± 8.0%, respectively, all of which were slightly higher but not significantly different than those in the Non-CAR-T group (84.6% ± 10.0%, P =.615; 77.4%± 11.5%, P =.256, respectively). Summary/Conclusion: CAR-T therapy bridging to allo-UCBT is a safe and effective therapeutic strategy for pediatric R/R B-ALL patients, and may have its special advantages in the MRD-positive subgroup. Compared with the non-CAR-T group, the CAR-T group had a lower incidence of severe GVHD.Keywords: CAR-T, relapsed/refractory, Umbilical cord blood transplant, Acute lymphoblastic leukemia